doi 10.15296/ijwhr.2016.02 http://www.ijwhr.net doi 10.15296/ijwhr.2015.27 OpenOpen Access Original Review Article

InternationalInternational Journal Journal of Women’s of Women’s Health Health and Reproduction and Reproduction Sciences Sciences Vol.Vol. 3, No.4, No. 3, July 1, January 2015, 126–131 2016, 4–7 ISSNISSN 2330- 4456 2330- 4456

FirstWomen Trimester on the Other Bleeding Side ofand War and Poverty: Outcomes: Its Effect Case- Controlon the Health Study of Reproduction 1 2* 2 BetülAyse Cevirme Yakıştıran,, Yasemin Tuncay Hamlaci Yüce*, Feride, Kevser Söylemez Ozdemir

Abstract AbstractWar and poverty are ‘extraordinary conditions created by human intervention’ and ‘preventable public health problems.’ War and Objectives:poverty have Themany purpose negative ofeffects this on study human was health, to determine especially women’sthe perinatal health. outcome Health problems and pregnancy arising due complication to war and poverty (preterm are delivery, pretermbeing observed prelabour as sexual rupture abuse of and membrane rape, all kinds [PPROM], of violence preeclampsia, and subsequent placental gynecologic abruption and obstetrics and intrauterine problems growth with physiological restriction [IUGR]) ofand threatened psychological . courses, and as the result of undesired but forced or obliged marriages and even rapes. Certainly, Materialsunjust treatment and Methods: such as being A total unable of 963 to gainpatients footing attended on the theland study. it is lived Of these, (asylum 493 seeker, women refugee, had threatenedetc.) and being miscarriage. deprived ofThe control groupsocial security,included citizenship 470 pregnants rights withoutand human first rights trimester brings vaginal about the bleeding. deprivation We ofcompared access to thehealth two services groups and according of provision to maternal of age, gravida,service intended parity, spontaneous for gynecology or and induced obstetrics. The purposehistory, ofpregnancy this article period, is to address livebirth effects or pregnancyof war and povertyloss, newborn on the health weight of and Apgar valuesreproduction after 1 of and women 5 minutes, and to newborns’offer scientific gender contribution for livebirth and solutions. and preterm deliveries. Results:Keywords: Incidence Poverty, Reproductiveof preterm delivery, health, War abortion, lower gestational fetal weight and preterm rupture of membrane was increased in threatened miscarriage group. Mean pregnancy period in threatened miscarriage group was 243 days; in control group was 263 days. There was adverse influence of maternal age and abortion history on outcomes in pregnancies with threatened miscarriage. However Introductionsex of the and Apgar values after 1 and 5 minutes were similarthought between that severetwo groups. military conflicts in Africa shorten ThroughoutConclusion: the Threatened history of miscarriage the world, is the an onesimportant who hadsituation theto predict expected both lifetime the maternal for more and than fetal 2outcomes years. In in general, late pregnancy. confrontedMaternal obstetric the bitterest history face on of previous poverty pregnancies and war had should al- be questioned.WHO had Itcalculated is therefore that essential 269 thousand to consider people these had pregnancies died as wayshigh beenrisk groupthe women. and provide As known careful poverty antenatal and care.war affects in 1999 due to the effect of wars and that loss of 8.44 mil- human health either directly or indirectly, the effects of lion healthy years of life had occurred (2,3). Keywords: Abortion, Uterine hemorrhage, Perinatal outcomes, Preterm labor this condition on health and status of women in the so- Wars negatively affect the provision of health services. ciety should not be ignored. This study intends to cast Health institutions such as hospitals, laboratories and light on the effects of war and poverty on the reproductive health centers are direct targets of war. Moreover, the wars Introductionhealth of women. For this purpose, the face of war affect- causeincrease the migration the risk of of qualified abortus healthimminens. employees, and Firsting the trimester women, bleedingthe problem is aof common immigration, symptom inequalities of preg - thus Thethe health purpose services of thishitches. study Assessments was to investigatemade indi- whether nancy,in distribution complicating of income 16%-25% based on of gender all pregnancies and the effects (1-3). cate thatthreatened the effect abortion of destruction makes in pregnancies the infrastructure high ofrisk, what Theof all four these major on the sources reproductive of nontraumatic health of women bleeding will inbe ear- healthis continuespoor neonatal for 5-10 outcome years even and after which the maternalfinalization character - lyaddressed. pregnancy are , miscarriage (threat- of conflictsistics change (3). Due these to resource results requirementsin our clinic. in Answer the re- to these ened, inevitable, incomplete or complete), implantation structuringquestions investments can change after ourwar, antepartum,the share allocated peripartum to and War and Women’s Health health has decreased (1). of pregnancy and cervical pathology. Physical and pelvic postpartum management. We aimed to investigate threat- Famine, synonymous with war and poverty, is clearer for examinationwomen; war meansshould deep be done disadvantages and further such with as fullthe dehelp- of Mortalitiesened abortion and Morbidities and pregnancy outcomes in our patients. imagingstruction, techniques, loss of future diagnosis and uncertainty and plan for women.of management Wars The ones who are most affected from wars are women and isare planned. conflicts that destroy families, societies and cultures children.Materials While anddeaths Methods depending on direct violence af- Abortusthat negatively imminens affect is the diagnosed health of communityas first trimester and cause vaginal fect theIn malethis retrospective population, the study indirect we examineddeaths kill children,493 patients with bleedingviolation withof human closed rights. cervix According and confirmed to the data with of fetalWorld heart womendiagnosis and elders of abortusmore. In imminens Iraq between who 1990-1994, were admitted in- to the rateHealth on Organizationultrasound (3,4).(WHO) Doppler and World confirmation Bank, in 2002 of fetal fant deathsDepartment had shown of Gynecology this reality inand its moreObstetric, bare formMedical Fac- cardiacwars had activity been among is reassuring the first as ten it reasonsindicates which that killedbleeding with ulty,an increase Ankara of University 600% (4). Thebetween war taking2007 andfive years2015. Threat- isthe not most related and caused to fetal disabilities. demise. After Civil lossesdetermining are at the the rate diag - increasesened the miscarriage child deaths was under defined age of 5as by positive 13%. Also fetal 47% heart rate of 90% within all losses (1). of all the refugees in the world and 50% of asylum seekers nosis,War has management many negative is important. effects on human Nearly health. 50% of One pregnan of - and displacedon people and are awomen history and of vaginal girls and bleeding 44% ref in- the first ciesthese end is itsin effectpregnancy of shortening loss; if pregnancythe average continues, human life. poor ugeestrimester. and asylum We seekers examined are children 470 singleton under the pregnant age of women maternalAccording and to the fetal data outcomes of WHO, such the averageas preterm human delivery life is (4), 18 (5).as control group with no symptoms of threatened miscar- preterm68.1 years prelabour for males ruptureand 72.7 ofyears membrane for females. (PPROM), It is being pre - As theriage result such of as wars vaginal and bleeding,armed conflicts, spotting women or pelvic are pain. , and intrauterine growth 493 women with threatened miscarriage were considered restriction (IUGR) may occur (1,3,5). It is known also that as group A. Control group (group B) included 470 preg- Received 12 December 2014, Accepted 25 April 2015, Available online 1 July 2015 maternal age (5,6), systemic diseases such as diabetes mel- nants without first trimester . We com- 1Department of Nursing, Sakarya University, Sakarya, Turkey. 2Department of Midwifery, Sakarya University, Sakarya, Turkey. litus,*Corresponding hypothyroidism, author: Yasemin infertility Hamlaci, Department treatment of Midwifery,(1), thrombo Sakarya- University,pared Sakarya, the Turkey. two groupsTel: +905556080628, according to maternal age, gravidity, philia,Email: [email protected] maternal weight and uterine structural anomalies parity, spontaneous or induced abortion history, pregnan-

Received 6 February 2015, Accepted 1 October 2015, Available online 1 January 2016

Department of Obstetric and Gynecology, Ankara University, Ankara, Turkey. *Corresponding author: Tuncay Yüce, Faculty of Medicine, Ankara University, Cebeci Campus, Mamak/Ankara, Turkey. Tel: +903125956405, Email: [email protected] Yakıştıran et al cy period, livebirth or pregnancy loss, newborn weight (88.3%) from group A, pregnancies continued after 24 and Apgar scores after 1 and 5 minutes, newborns’ gender weeks’ of gestation. The relationship between vaginal for livebirth and preterm deliveries. bleeding and preterm delivery subtypes was also eval- Outcome measures included preterm labour, fetal birth uated. In this study population 94 patients (21.6%) of weight, Apgar scores after 1 and 5 minutes, livebirth or preterm cases delivered between 24-37 weeks’ gestation. pregnancy loss, sex of the fetuses, and previous maternal In preterm deliveries; 60 patients (63.8%) delivered be- obstetric history (gravidity, parity, spontaneous abortion, tween 34-37 weeks’ gestation; 21 patients (22.3%) between induced abortion history). The assessment of all patients 28-34 weeks’ gestation and 13 patients (13.8%) between included maternal disease; hereditary thrombophilia, 24-28 weeks’ gestation. chronic hypertension and diabetes mellitus, hypothy- In group A; hereditary thrombophilia was found in 20 roidism, preeclampsia and fetal abnormality. Hereditary patients during pre-pregnancy assessment. These patients thrombophilia included thrombosis, G1691A mutation in had used low molecular weight heparin during whole the factor 5 gene, G20210A mutation in the prothrombin pregnancy period. Twenty-nine patients were hypothy- gene, C677T mutation and A1298C mutation in MTHFR roid, 4 of them complicated with previa and preg- gene, antithrombin 3, protein C and S deficiency. nancy induced hypertension occurred in two patients. 11 The inclusion criteria were singleton pregnancies com- of them had different diseases such as asthma (one pa- plicated with vaginal bleeding at less than 14 weeks’ ges- tient), psychosis (3 patients), cervical cancer (1 patient), tation with positive fetal heart pulsations detected with cardiac surgery (2 patients), chronic hypertension (3 pa- ultrasound. The was estimated from last tients), pregestational diabetes mellitus (2 patients), and menstrual period and the first trimester ultrasound. If the sarcoidosis (1 patient). Also 29 patients of group A were self reported last menstrual period was >7 days from the hypothyroid and 5 of them had spontaneous abortion. calculated ultrasound last menstrual period; then the ul- Women in the threatened miscarriage group; 10 of them trasound was used to assign the gestational age. had complication with placenta previa; 5 of them com- Multiple pregnancies, patient who had gynecological pa- plicated with preeclampsia. And 13 of these patients had thologies such as polyps, cervicitis or cervical myomas pregnancy induced hypertension during the pregnancy. were excluded. All patients’ pregnancy period were re- Only one of them had intrauterine exitus and was corded and preterm delivery ( <37 weeks’ gestation) and terminated after that. Also cholestasis was observed in abortion (<24 weeks’ gestation) were accepted. three patients. In early gestational weeks 5 major fetal ab- Data were analysed with SPSS.21.0. The statistical analysis normalities were determined with ultrasound scan. Three of the differences between the patient and control groups of them were trisomy 21 and all were terminated. The for the parameters showing normal distribution was done other abnormalities included Walker-Warburg syndrome with a parametric test “independent-samples Student’s t and cystic hygroma; these pregnancies did not terminate test.” Used as a non-parametric test, the “Mann-Whitney because of absence of parental consent. Only one placen- U” was used to make comparisons among the parame- tal abruption occurred in 33 weeks’ gestation. IUGR in 9 ters that did not demonstrate normal distribution. Pear- pregnancies and mellitus in 13 pa- son chi-square tests (non-parametric) were performed to tients were diagnosed. test statistical significance of the differences in propor- As seen below, in group A with threatened abortion, ma- tions. A value of P < 0.05 was considered to be statistically ternal age was higher than control group and statistical- significant. ly significant. There were no differences in gravidity be- tween two groups. However, there were statistically differ- Results ences in parity and spontaneous abortion rates. In control We examined the patients with threatened miscarriage group, pregnancy period is more longer than group A diagnosis who applied to the clinic because of the first tri- expectedly. Gender of fetuses were similar in both groups. mester vaginal bleeding between 2007 and 2015. A total Because of the higher rates of preterm delivery in group of 963 patients attended the study. Of these, 493 women A; birth weight was lower in this group when compared had threatened miscarriage (group A). The control group with control group. However interestingly APGAR scores (group B) included 470 pregnants without first trimester in first and 5 minutes did not change. vaginal bleeding. Results for the two groups are presented In group A cervical cerclage was performed in only one on Table 1. patient who had history of cervical conization. In eight pa- In group A there were two groups; the first was with tients preterm premature rupture of membrane occurred. livebirth and the second was spontaneous abortion. Both In group A, there were two groups; livebirth and spon- of these groups were compared with each other in regard taneous abortion groups. When we compared these two to maternal age, gravidity, parity, spontaneous or induced groups maternal age, gravidity, parity, presence of sponta- abortion history. However there were not statistically sig- neous or induced abortion before and livebirth had sim- nificant differences among groups. ilar rates. In threatened abortion group, there was no sta- In 58 patients (11.7%) from group A, terminated their tistically significance between abortion or livebirth during pregnancies with spontaneous abortion. In 435 patients pregnancy (Table 2).

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Table 1. Comparison of Outcomes of Pregnancies in Control and ond trimester bleeding were similar (4,10). Case Groups Preterm delivery and PPROM rates were increased in Threatened Control P Valuea the threatened miscarriage group (4,7,9,11,12). Because Abortion (n = 493) (n = 470) Maternal age 33.5±5.4 28.8±5.2 <0.001 of increased free iron deposits from subchorionic bleed- ing, hydroxyl radical is catalyzed damaging the mem- Gravida 2.1±1.2 1.9±1.1 0.077 branes (4,7). The other point in PPROM’s etiology is the Parity 0.51±0.75 0.68±0.94 0.006 chronic inflammatory reaction within the decidua and Spontanous abortion 0.51±0.86 0.18±0.5 <0.001 placental membranes with weakening and rupture of the Dilatation curettage 0.14±0.47 0.09±0.42 0.11 membranes. Investigators have speculated that decidual Livebirth 0.46±0.71 0.65±0.78 0.002 thrombosis, ischemia and necrosis result in vaginal bleed- Pregnancy period 243±59 263±35 <0.0001 ing along with inflammatory response and thrombin for- mation. Thrombin is a uterotonic agent and may cause Birth weight 3115±665 3239±619 0.005 preterm labor during late pregnancies and spontaneous Gender (f/m) 180/206 188/262 0.147 abortion during early weeks of gestation (3,9,13,14). Sub- Apgar 1 min 8±(0-9) 8±(0-9) 0.080 chorionic hematoma can result in a nidus which may be- (median ± min-max) come infected and cause preterm Apgar 5 min 9±(0-10) 9(0-10) 0.060 (median ± min-max) (13). In Saraswat et al study similar results were demon- strated for PPROM (3). Preterm delivery 94/493 40/470 <0.001 Both preterm delivery and PPROM are related with low Abortus 58/493 20/470 <0.001 birth weight as predictable factors. Our study demon- a P < 0.05 is significant. strated that the fetal weight was lower in the case than control group. It is related with births at earlier gestations Table 2. Spontaneous Abortion and Livebirth Groups in Group A (7,15). Neonatal intensive care unit admission for low Livebirth Abortion birth weight fetuses was increased because of prematu- P Value (n = 435) (n = 58) rity complications such as respiratory distress (7). The Age 33.3±5.3 34.8±6.1 0.11 objective parameter of fetal outcome cord blood sample Gravida 2.1±1.2 2.1±1.4 0.21 was not detected for fetal pH. But we recorded APGAR scores after one and five minutes. In our study interesting- Parity 0.50±0.75 0.55±0.94 0.25 ly, we did not find relationship between the control group Abortion history 0.51±0.86 0.44±0.78 0.55 and threatened miscarriage group for Apgar scores. As an Dilatation curettage history 0.13±0.46 0.24±0.51 0.075 opinion, lower Apgar scores after 1 and 5 minutes were ex- Livebirth 0.46±0.70 0,48±0.78 0.61 pected in threatened abortion group because of increased rates of preterm delivery. a P < 0.05 is significant. Additionally in threatened miscarriage group, maternal obstetric history (gravidity, parity and spontaneous or Discussion induced abortion, intrauterine exitus) was important for This study indicates that women who have vaginal bleed- examinations during . With previous threat- ing in the first trimester are at increased risks of later ened , this pregnancy may be more compli- pregnancy complications; especially preterm delivery, cated with preterm delivery, PPROM, lower birth weight shortened mean pregnancy period, lower gestational fetal (1,2,4,9,13). In literature also this situation was related weight and preterm rupture of membrane (1,2,7). Mean with pregnancy induced hypertension and preeclampsia pregnancy period in threatened miscarriage group was and lower Apgar scores with poor previous obstetric his- 243 days; in control group it was 263 days. There was ad- tory (5). verse influence of maternal age and abortion history on Bleeding amount and characteristics are related with poor outcomes in pregnancies with threatened miscarriage maternal and fetal outcome (7,10,12,14) which was we did (6,8). However sex of the fetuses and Apgar scores after 1 not record. Our study was retrospective so that we inves- and 5 minutes were similar between two groups. tigated only patient records. If subchorionic hematoma Bleeding during first trimester was associated with in- had occurred, we recorded the size of the hematoma in creased risk of preterm delivery (4). Because of impaired the ultrasound scanning forms. Our sample size for hema- implantation and invasive trophoblasts, spontaneous toma wasn’t enough so we did not include it. All patients abortion may occur in early pregnancy while preterm de- data were obtained from computer database and patients’ livery, PPROM, placental ablation and preeclampsia may files so that number of patients are under estimated. In happen in later period (2,4,9). Our results were similar our clinic, very few patients who were complicated with to those reported before by Hossain et al (4). According threatened abortion were hospitalized; so very few pa- to these studies, the first and second trimester bleeding tients were included in this investigation. We included complications are more likely than only the first trimester only those patients that had full data both n computer da- bleeding. But only risk of preterm delivery in first or sec- tabase and patients files.

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Conclusion A, Liversedge N, Taylor M. The influence of In conclusion threatened miscarriage is an important situ- maternal age on the outcomes of pregancies ation to predict late pregnancy results; both maternal and complicated by bleeding at less then 12 weeks. Acta fetal outcomes. Maternal obstetric history about previous Obstetricia et Gynecologica 2009;88(1):116-118. pregnancies should be questioned. It is therefore accept- doi:10.1080/00016340802621005. able to consider these pregnancies as high risk group for 7. Johns J, Jauniaux E. Threatened miscarriage which antenatal care should be performed carefully. as a predictor of obstetric outcome. Obstet Gynecol. 2006;107:845-850. doi:10.1097/01. Ethical issues AOG.0000206186.91335.9a. An inquiry was made and sent to Ankara University 8. Yang J, Savitz DA, Dole N, et al. Predictors of vaginal Ethics Commission. Due to nature of non-confidential bleeding during the first two trimesters of pregnancy. data required for study, retrospective nature of data col- Paediatric Perinatal Epidemiol. 2005;19(4):276-283. lection, ethics approval and patient consent was deemed doi: 10.1111/j.1365-3016.2005.00655.x. unnecessary. 9. Hackney DN, Glantz JC. Vaginal bleeding in early pregnancy and : systematic review and Conflict of interests analysis of heterogeneity. J Maternal-Fetal Neonatal None to be declared. Med. 2011;24(6):778-86. doi:10.3109/14767058.2010 .530707. Financial support 10. Velez Edwards DR, Baird DD, Hasan R, Savitz DA, Our study did not use funds from any authority. Hartmann KE. First trimester bleeding characteristics associate with increased risk of preterm birth: data Acknowledgments from a prospective pregnancy cohort. Hum Reprod. None to be declared. 2012;27(1):54-60. doi:10.1093/humrep/der354. 11. Yang J, Savitz DA. The effect of vaginal bleeding References during pregnancy on preterm and small for 1. Evrenos A, Güngör A, Gülerman C, Cosar E. Obstetric gestational age births: US national Maternal and outcomes of patients with abortus imminens in the Infant Health Survey, 1988. Paediatric Perinatal first trimester. Arch Gynecol Obstet. 2014;289(3):499- Epidemiol. 2001;15(1):35-39. doi:10.1046/j.1365- 504. doi:10.1007/s00404-013-2979-5. 3016.2001.00318.x. 2. Lykke JA, Dideriksen KL, Lidegaard O, Langhoff-Roos 12. Mulik V, Bethel J, Bhal K. A retrospective population J. First trimester vaginal bleeding and complications based of primigravid women on the potential effect later in pregnancy. Obstet Gynecol. 2010;115(5):935- of threatened miscarriage on obstetric outcome. J 944. doi: 10.1097/AOG.0b013e3181da8d38. Obstet Gynecol. 2004;24(3):249-253. doi:10.1080/01 3. Saraswat L, Bhattacharya S, Maheshwari A, 443610410001660724. Bhattacharya S. Maternal and perinatal outcome 13. Rosen T, Kuczynski E, O’Neill LM, Funai EF, in women with threatened miscarriage in the first Lackwood CJ. Plasma levels of thrombin- trimester: a systematic review. BJOG. 2010;117:245- antithrombin complexes predict preterm premature 257. doi:10.1111/j.1471-0528.2009.02427.x. rupture of the fetal membranes. J Maternal- Fetal Med. 4. Hossain R, Harris T, Lohsoonthorn V, Williams 2001;10(5):297-300. doi:10.1080/jmf.10.5.297.300. M. Risk of preterm delivery in relation to vaginal 14. Yang J, Hartmann KE, Savitz DA, et al. Vaginal bleeding in early pregnancy. Eur J Obstet Gynecol bleeding during pregnancy and preterm birth. Am Reprod Bio. 2007;135(2):158-163. doi.org/10.1016/j. J Epidemiol. 2004;160(2):118-125. doi:10.1093/aje/ ejogrb.2006.12.003. kwh180. 5. Dadkhah F, Kashanian M, Eliasi GA. Comparison 15. Sun L, Tao F, Hao J, Su P, Liu F, Xu R. First trimester between the pregnancy outcome in women bleeding and adverse pregnancy outcomes among both with or without threatened abortion. Early Chinese women: from a large cohort study in China. J Hum Dev. 2010;86(3):193-196. doi:10.1016/j. Maternal-Fetal Neonatal Med. 2012;25(8):1297-1301. earlhumdev.2010.02.005. doi:10.3109/14767058.2011.632034. 6. Gitau G, Liversedge H, Goffey D, Hawton

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